Alterations of the mitochondrial enzyme, monoamine oxidase (MAO), in brain has been implicated in the etiology of a variety of behavioral disorders including schizophrenia and uni-and bipolar depression. Accordingly, the project in my laboratory has as its objectives to (1) characterize the properties of human brain type A and B MAO and to (2) understand the effects of drugs and hormones on these isoenzymes. To date, we have extensively studied the kinetic properties of the B form of human brain MAO. The reaction sequence proceeds via a double-displacement mechanism which can account for many of the unique features of this enzyme in relation to drug binding and inhibition and in reference to a variety of other biochemical parameters. Additional studies have revealed that the kinetic properties of both the A and B forms of MAO are altered on solubilization with the non-ionic detergent, Triton X-100. These studies suggest that the lipid matrix in the outer mitochondrial membrane helps regulate MAO activity in vivo. Other studies have demonstrated that the hydrazine derivatives, benzylhydrazine and phenylhydrazine, selectively inhibit the B form of human brain MAO. Although both drugs are selective in this process, the affinity of phenylhydrazine for MAO type B is almost 100 times less than that of benzylhydrazine, or the clinically important antidepressant agent, phenelzine.